《Structural Analysis and Development of Notum Fragment Screening Hits》 was written by Zhao, Yuguang; Mahy, William; Willis, Nicky J.; Woodward, Hannah L.; Steadman, David; Bayle, Elliott D.; Atkinson, Benjamin N.; Sipthorp, James; Vecchia, Luca; Ruza, Reinis R.; Harlos, Karl; Jeganathan, Fiona; Constantinou, Stefan; Costa, Artur; Kjaer, Svend; Bictash, Magda; Salinas, Patricia C.; Whiting, Paul; Vincent, Jean-Paul; Fish, Paul V.; Jones, E. Yvonne. Safety of 1-Chloro-3-iodobenzeneThis research focused ontriazzole pyrazole benzimidazole synthesis SAR Notum Wnt signaling; Diamond-SGC Poised Library (DSPL); Notum inhibitors; Wnt signaling; fragment screening; hit-to-lead development. The article conveys some information:
The Wnt signaling suppressor Notum is a promising target for osteoporosis, Alzheimer′s disease, and colorectal cancers. To develop novel Notum inhibitors, we used an X-ray crystallog. fragment screen with the Diamond-SGC Poised Library (DSPL) and identified 59 fragment hits from the anal. of 768 data sets. Fifty-eight of the hits were found bound at the enzyme catalytic pocket with potencies ranging from 0.5 to >1000 μM. Anal. of the fragments′ diverse binding modes, enzymic inhibitory activities, and chem. properties led to the selection of six hits for optimization, and five of these resulted in improved Notum inhibitory potencies. One hit, 1-phenyl-1,2,3-triazole 7, and its related cluster members, have shown promising lead-like properties. These became the focus of our fragment development activities, resulting in compound 7d (I)h IC50 0.0067 μM. The large number of Notum fragment structures and their initial optimization provided an important basis for further Notum inhibitor development. In the experimental materials used by the author, we found 1-Chloro-3-iodobenzene(cas: 625-99-0Safety of 1-Chloro-3-iodobenzene)
1-Chloro-3-iodobenzene(cas: 625-99-0) belongs to organic iodides. The carbon-iodine bond is weaker than other carbon-halogen bonds due to the poor electronegative nature of the iodine atom. Safety of 1-Chloro-3-iodobenzene Alkyl iodides react at a faster rate than alkyl fluorides due to the weak C-I bond.
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com